A growing understanding of human genetics holds the promise to dramatically change health care through customized preventative care and treatments. In his upcoming Stanford Continuing Studies course, "Your Genes and Your Health," Douglas Brutlag, PhD, will discuss how the billions of bits in our biological code shape who we are and how tapping into this information can reveal a lot about your potential health and future well-being.
As Brutlag explains in the following Q&A, understanding the way specific genetic variants influence disease risk can lead to reduced health care costs and a new approach to a healthy lifestyle.
What percentage of our health is dictated by our genetics, and what portion can be attributed to a person's behavior or environment?
The percentage of our health dictated by our genetics and the faction by behavior and environment depends on individual diseases. Some diseases are entirely genetic and they are called 100 percent penetrant. Diseases such as Huntington's disease, cystic fibrosis, sickle cell anemia, Tay-Sachs disease and Downs syndrome are purely genetic. Other, more complex diseases such as Type 2 diabetes or rheumatoid arthritis have a significant behavioral component. That means that even if a person has a genetic predisposition towards the disease there is a lot one can do behaviorally to prevent it.
Complex or multifactorial diseases often have several genetic components as well as several behavioral components. For example, there are now at least a dozen known genes that can contribute to Type 2 diabetes. This is because there are many pathways that lead to the disease. Decreased production of insulin, decreased secretion of insulin and decreased response to insulin are the most common. On the other hand, many behavioral aspects can contribute to causing or exacerbating the disease. Obesity and sedentary life style are but two of them. Many other diseases, such as lung cancer, are nearly entirely behavioral. Others, such as most infectious diseases, are entirely environmental.
How can understanding the way specific genetic variants influence individuals' disease risk enable awareness and possible prevention or treatment?
If someone knows that they have genes predisposing them to a particular disease, then they can be more vigilant to other symptoms of that disease and also discuss further clinical tests for the disease with their doctor. For example, if someone has certain alleles of the gene for clotting factor F5, it could be an indication that the person might be at a high risk of developing deep vein thrombosis (DVT) and one should perform a test of their thrombin levels. This is very important as DVT can lead to strokes and pulmonary embolisms resulting in death.
Other examples are familial breast cancer. If a person has a family history of breast cancer and genetic tests indicate that they have one of the BRCA 1 or BRCA 2 mutations, then they should make sure that they have regular mammography exams. Familial breast cancer is one of the complex diseases that is not 100 percent penetrant. Twenty percent of individuals carrying these mutations will not get breast cancer or ovarian cancer during their entire life. Nevertheless, all such individuals should be much more vigilant than those without these genes.
Finally, if one has two or three of the genes that predispose them to Type 2 diabetes, they should watch their weight, exercise regularly and have their blood glucose measured routinely. Also knowing the type of genetic defects associated with a person's Type 2 diabetes can help in planning their treatment. There are genetic loci that reduce the number of insulin producing cells in the pancreas that are best treated with drugs that stimulate insulin production from the remaining cells. Obese people often become insulin resistant and they would need a different or additional treatment.
How can knowing one's own genetic profile help reduce health care costs and motivate patients to make healthier decisions?
Preventive medicine is always the best and least expensive medicine. We currently use vaccines to prevent many infectious diseases. This is far less expensive and much better for the patient than using antibiotic or anti-viral treatments to try to cure an infection. The risks are also substantially lower with vaccines. Much of the cost of the current health care is due to expensive diagnostic methods and interventions for patients who already have a disease. So preventing the disease in the first place is by far, the best way to reduce health care costs.
Hopefully, genomics and genetic testing will do for inherited disease what vaccines have done for infectious disease. I see genomics as being the way toward preventing the manifestations of inherited disease. More importantly, the cost of sequencing is coming down so fast that in the next three to five years we will be able to determine the complete genome sequence of every individual at birth for less than $1,000. This genomic information, coupled with our knowledge of the genes causing disease mentioned above will give people a genetic roadmap of their potential inherited diseases. This will empower doctors to design specific tests for each person to track his progress along their genetic roadmap as well as recommendations for behaviors likely to improve one's health by dimishing the chance of a given disease.
Preventing disease will also become the responsibility of the patient. He will know what the risks he takes if he smokes, over-eats or leads a sedentary life style. The risks will be personalized based on his own genetics.
A 2009 survey showed that a significant number of doctors don't have the knowledge necessary to interpret genetic test results and use the information to guide medical decisions. Beyond primary care doctors, what other resources, tools or members of the health-care community can patients use to understand genetic disease?
We are in state of transition where we need more physicians in the medical genetic specialty and more trained genetic counselors. Interpreting the current genetic tests requires knowledge of statistics, probability and utility functions. However, I see a time in the near future where we know the causal mutations in the human genome and we understand the molecular basis for most diseases. Then the genetic diagnosis will move from a probabilistic analysis to a more deterministic or rule based approach that could provide the doctor directly with the correct advice. Even then, I think that we will want to have medical genetic specialists and genetic counselors in every hospital and clinic.
Many medical schools, including Stanford, are now training their students in the interpretation of genetic and genomic data. Yet it will take several years to provide the level of expertise that will be needed to use this kind of data. Hopefully there will be a time soon when the genetic tests will appear as just another clinical test that doctors order for their patients.
You use data from your own genome analysis to demonstrate to students how to look at their own ancestry, family relationships and inherited diseases. How has the experience of analyzing your own DNA affected your health-care decisions?
Greatly. I am a type 2 diabetic and by knowing the alleles of my specific genes that are associated with my disease, I have been able to tailor my drug regime to best fit my genetic situation. It has also permitted me to eliminate some of the more expensive diabetic drugs I really did not need and now I use only less expensive generic drugs, lowering my pharmacy bill tremendously. Similarly these tests have helped the rest of my family and their physicians become aware of potential inherited disease, long before debilitating symptoms have appeared.
Previously: Could patients' knowledge of their DNA lead to better outcomes?, A conversation about the benefits and limitations of direct-to-consumer genetic tests, Controversial class primes students in genomics, Stanford TA weighs in on what students learned by being genotyped, Stanford students discuss studying their own genotypes and Genotype testing for medical, graduate students